ANGUSTA Tablet Ref.[27660] Active ingredients: Misoprostol

Angusta should only be administered by trained obstetric personnel in a hospital setting where facilities for continuous fetal and uterine monitoring is available and the cervix should be assessed carefully before product use.

Angusta can cause excessive uterine stimulation.

If uterine contractions are prolonged or excessive, or there is a clinical concern for the mother or baby, additional Angusta tablets should not be administered. If excessive uterine contractions continue, treatment according to local guidelines should be started.

In women with pre-eclampsia, evidence or suspicion of foetal compromise should be ruled out (refer to section 4.3). There are no or limited clinical data with misoprostol in pregnant women with severe pre-eclampsia marked by Haemolytic anaemia; Elevated Liver enzymes; Low Platelet count (HELLP) syndrome, other end organ affliction or CNS findings other than mild headache.

Chorioamnionitis may necessitate fast delivery. Decisions regarding antibiotic treatment, induced labour or caesarean section will be at the physician’s discretion.

There are no or limited clinical data with misoprostol in women whose membranes have been ruptured for more than 48 hours prior to administration of misoprostol.

There may be synergistic/additive effects of misoprostol and oxytocin. Concomitant administration of oxytocin is contraindicated. See section 4.3. Angusta is eliminated after 4 hours. See section 5.2. It is recommended to wait 4 hours after last dose of Angusta before administration of oxytocin (see sections 4.2 and 4.5).

There are no or limited clinical data with misoprostol in multiple pregnancies. There are no or limited clinical data with misoprostol in grand multiparity.

There are no or limited clinical data with misoprostol before week 37 of gestation (see section 4.6).

Angusta should be used only when induction of labour is clinically indicated.

There are no or limited clinical data with misoprostol in pregnant women with bishop score (mBS) >6.

An increased risk of post-partum disseminated intravascular coagulation has been described in patients whose labour has been induced by any physiological or pharmacological method.

A lower dose and/or prolonged dosing intervals should be considered in pregnant women with renal or hepatic impairment (see section 5.2).

No interaction studies have been performed with Angusta.

Concurrent use of oxytocic drugs or other labour induction agents is contraindicated due to the potential of increased uterotonic effects (see sections 4.2, 4.3, 4.4 and 5.2).

Fertility

Studies of fertility and embryo development in rats have shown that misoprostol may have an impact on implantation and resorption. This is, however, considered of no relevance for the indicated use of Angusta in late pregnancy.

Pregnancy

Angusta has been studied in pregnant women ≥37 weeks of gestation.

Angusta should only be used prior to 37 weeks of gestation if medically indicated (see section 4.4).

Angusta is used for labour induction at a low misoprostol dosage for a short period of time at the very end of pregnancy. When used at that time of pregnancy, there is no risk of foetal malformations. Angusta should not be used at any other time during pregnancy: a threefold increased risk of foetal malformations (including Moebius syndrome, amniotic band syndrome and central nervous system anomalies) has been reported in pregnancies exposed to misoprostol in first trimester.

Breast-feeding

No studies have been performed to investigate the amount of misoprostol acid in colostrum or breast milk following the use of Angusta.

Misoprostol has been detected in human milk following oral administration of misoprostol in tablet form.

Pharmacokinetic trials reveal that oral misoprostol (at dose levels of 600 µg and 200 µg) is excreted into breast milk with drug levels that rise and fall very quickly. The maximum concentration of misoprostol acid in expressed breast milk was achieved within 1 hour after dosing and was 7.6 pg/ml (% CV 37%) and 20.9 pg/ml (% CV 62%) after single 200 mcg and 600 mcg misoprostol administration, respectively. Negligible amounts of misoprostol acid remain in maternal plasma after 5 half-lives (3.75 hours), and even lower concentrations will remain in breast milk. Breast-feeding can start 4 hours after the last dose of Angusta is administered.

Not relevant.

The undesirable effects listed in the table below have been reported in 41 trials where a total of 3,152 women were exposed to oral misoprostol at doses of 20-25 µg every 2 hours or 50 µg every 4 hours. In addition, adverse events reported in a compassionate use program, where approximately 29,000 women have been exposed to Angusta for induction of labour are also listed.

^* Neonatal adverse reaction
¹ ADRs which were reported from the compassionate use programme including birth hospitals in Denmark, Norway and Finland, where approximately 29,000 women have been exposed to Angusta for induction of labour.
² Nausea was common with 25 µg every 2 hours and very common with 50 µg every 4 hours.
³ Vomiting was common with 25 µg every 2 hours and very common with 50 µg every 4 hours.
⁴ Uterine hyperstimulation was reported both with and without foetal heart rate changes.
⁵ Postpartum haemorrhage was very common with 25 µg every 2 hours and common with 50 µg every 4 hours.
⁶ Apgar score low was uncommon with 25 µg every 2 hours and common with 50 µg every 4 hours.
⁷ Foetal heart rate abnormal was reported in connection with uterine hyperstimulation.

Uterine hyperstimulation with foetal heart rate changes was uncommon with 25 µg every 2 hours and common with 50 µg every 4 hours.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme Website: www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple Store.

Not applicable.